We propose to investigate the metabolism of polycyclic hydrocarbons in liver, lung, and skin of rats and human beings. The major areas of research will be as follows: I. Furthr studies on the enzyme systems involved in the metabolism of polycyclic hydrocarbons an on their relative importance in the production and removal of reactive intermediates. II. Studies on the induction of enzymes involved in xenobiotic metabolism by transtilbene oxide. III. Studies on DNA binding, including studies on the manner in which reactive metabolites of polycyclic hydrocarbons travel from the site of generation to the "target site": the structure of the adduct formed between reactive intermdiates of benzpyrene metabolism and DNA: and binding of reactive metabolites of benzpyrene to mitochondrial DNA. IV. Studies on the repair of DNA modified by reaction with benzpyrene metabolites and examination of the possible induction of repair enzymes. V. Exchange of metabolites between organs and the possible role of the liver in extrahepatic carcinogenesis.